Developmental regulation of B lymphocyte immune tolerance compartmentalizes clonal selection from receptor selection.
B lymphocyte development is a highly ordered process that involves immunoglobulin gene rearrangements, antigen receptor expression, and a learning process that minimizes the development of cells with reactivity to self tissue. Two distinct mechanisms for immune tolerance have been defined that operate during early bone marrow stages of B cell development: apoptosis, which eliminates clones of cells, and receptor editing, which spares the cells but genetically reprograms their autoreactive antigen receptors through nested immunoglobulin L chain gene rearrangements. We show here that sensitivity to antigen-induced apoptosis arises relatively late in B cell development and is preceded by a functionally distinct developmental stage capable of receptor editing. This regulation compartmentalizes clonal selection from receptor selection.
Melamed
D
D
Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Benschop
R J
RJ
Cambier
J C
JC
Nemazee
D
D
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D017637:Clonal Deletion; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000276:immunology*; D019254:Genes, bcl-2 / Q000276:immunology; D006183:H-2 Antigens / Q000032:analysis; D007108:Immune Tolerance / Q000276:immunology*; D007072:Immunoglobulin D / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*
D001324:Autoantigens; D004268:DNA-Binding Proteins; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2; D002118:Calcium